Osterud B
Institute of Medical Biology, University of Tromsø, Norway.
Blood Coagul Fibrinolysis. 1990 Jun;1(2):175-81.
The role of factor VII in the haemostatic mechanism as well as thrombosis has recently gained new interest. Today's concept that factor VII may be a key regulator in the initiation of blood coagulation is based on studies that provide new evidence for a mandatory activation of factor VII to factor VIIa in blood. Exposure of thromboplastin to the circulation may not trigger activation of blood coagulation before the one chain factor VII is converted to the active two chain form of factor VIIa. A hypothetical model is proposed for the initiation and subsequent activation steps of the blood coagulation process. In this model, it is suggested that circulating activators of factor VII activate inactive complexes of thromboplastin-factor VII. Subsequently, newly generated factor Xa will accelerate this reaction and thereafter be the most potent activator of factor VII. This model would also fit with the clinical observation that moderate factor VII deficiency may be associated with thrombotic episodes discussed in this communication. This article also discusses the role of recombinant factor VIIa in the treatment of factor VIII deficiency patients with acquired factor VIII inhibitors, factor VII and ischemic heart disease and the factor VII-phospholipid complex, and the regulation of the thromboplastin-factor VIIa complex by factor Xa and extrinsic pathway inhibitor (EPI).
最近,因子VII在止血机制以及血栓形成中的作用引发了新的关注。如今认为因子VII可能是血液凝固起始过程中的关键调节因子,这一观点基于多项研究,这些研究为血液中因子VII强制性激活为因子VIIa提供了新证据。在单链因子VII转化为活性双链形式的因子VIIa之前,凝血酶原暴露于循环系统可能不会触发血液凝固的激活。本文提出了一个关于血液凝固过程起始及后续激活步骤的假设模型。在该模型中,有人认为循环中的因子VII激活剂会激活凝血酶原 - 因子VII的无活性复合物。随后,新生成的因子Xa会加速这一反应,并且此后将成为因子VII最有效的激活剂。该模型也符合本文所讨论的临床观察结果,即中度因子VII缺乏可能与血栓形成事件有关。本文还讨论了重组因子VIIa在治疗获得性因子VIII抑制剂的因子VIII缺乏患者、因子VII与缺血性心脏病以及因子VII - 磷脂复合物方面的作用,以及因子Xa和外源性途径抑制剂(EPI)对凝血酶原 - 因子VIIa复合物的调节作用。